The relation of daily energy expenditure (EE) and maximal oxygen uptake(˙VO2max) to plasma fibrinogen with reference to DNA polymorphism was analyzed in a random sample of men (N = 189), age 50-60. Fibrinogen polymorphism was detected using polymerase chain reaction (PCR) and digestion with HindIII and BclI (β-fibrinogen), and TaqI(α-fibrinogen) restriction enzymes. Mean ˙VO2max was 29.4 ml·kg-1·min-1 (95%CI 28.5; 30.2) and mean daily EE was 179 kJ·kg-1·d-1 (173; 186) and were similar in all fibrinogen genotypes. Plasma fibrinogen was 3.26 g·l-1(3.18; 3.34) and did not associate with fibrinogen polymorphisms. Both EE and˙VO2max related inversely to fibrinogen level (r = -0.24,P < 0.001). Strongest predictors of plasma fibrinogen were˙VO2max in TaqI 800 bp homozygotes, and EE together with smoking in TaqI 900 bp homozygotes. The predictive role of ˙VO2max was marginal in the common β-fibrinogen genotypes, whereas physical activity level explained up to 9% of the variance in the less frequent genotypes. These data suggest that the association of ˙VO2max and EE with plasma fibrinogen varies across the fibrinogen genotypes.